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WO1999062581A2 - Systeme clos de reinhalation permettant de conserver les memes dosages lors d'une ventilation par liquide - Google Patents

Systeme clos de reinhalation permettant de conserver les memes dosages lors d'une ventilation par liquide Download PDF

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Publication number
WO1999062581A2
WO1999062581A2 PCT/US1999/012133 US9912133W WO9962581A2 WO 1999062581 A2 WO1999062581 A2 WO 1999062581A2 US 9912133 W US9912133 W US 9912133W WO 9962581 A2 WO9962581 A2 WO 9962581A2
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WIPO (PCT)
Prior art keywords
breathing circuit
ventilator
circuit
oxygen
fluid communication
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Ceased
Application number
PCT/US1999/012133
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English (en)
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WO1999062581A3 (fr
Inventor
Dwayne Westenkow
Joseph A. Orr
Scott Kofoed
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Axon Medical Inc
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Axon Medical Inc
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Publication date
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Priority to AU44111/99A priority Critical patent/AU4411199A/en
Publication of WO1999062581A2 publication Critical patent/WO1999062581A2/fr
Publication of WO1999062581A3 publication Critical patent/WO1999062581A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M16/00—Devices for influencing the respiratory system of patients by gas treatment, e.g. ventilators; Tracheal tubes
    • A61M16/0054—Liquid ventilation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M16/00—Devices for influencing the respiratory system of patients by gas treatment, e.g. ventilators; Tracheal tubes
    • A61M16/0057—Pumps therefor
    • A61M16/0081—Bag or bellow in a bottle
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M16/00—Devices for influencing the respiratory system of patients by gas treatment, e.g. ventilators; Tracheal tubes
    • A61M16/20—Valves specially adapted to medical respiratory devices
    • A61M16/208—Non-controlled one-way valves, e.g. exhalation, check, pop-off non-rebreathing valves
    • A61M16/209—Relief valves
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M16/00—Devices for influencing the respiratory system of patients by gas treatment, e.g. ventilators; Tracheal tubes
    • A61M16/0057—Pumps therefor
    • A61M16/0078—Breathing bags
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M16/00—Devices for influencing the respiratory system of patients by gas treatment, e.g. ventilators; Tracheal tubes
    • A61M16/10—Preparation of respiratory gases or vapours
    • A61M16/1005—Preparation of respiratory gases or vapours with O2 features or with parameter measurement
    • A61M16/1015—Preparation of respiratory gases or vapours with O2 features or with parameter measurement using a gas flush valve, e.g. oxygen flush valve
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M16/00—Devices for influencing the respiratory system of patients by gas treatment, e.g. ventilators; Tracheal tubes
    • A61M16/22—Carbon dioxide-absorbing devices ; Other means for removing carbon dioxide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M16/00—Devices for influencing the respiratory system of patients by gas treatment, e.g. ventilators; Tracheal tubes
    • A61M16/10—Preparation of respiratory gases or vapours
    • A61M16/1005—Preparation of respiratory gases or vapours with O2 features or with parameter measurement
    • A61M2016/102—Measuring a parameter of the content of the delivered gas
    • A61M2016/1025—Measuring a parameter of the content of the delivered gas the O2 concentration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2202/00—Special media to be introduced, removed or treated
    • A61M2202/04—Liquids
    • A61M2202/0468—Liquids non-physiological
    • A61M2202/0476—Oxygenated solutions

Definitions

  • the present invention relates to improvements in ventilation devices that are especially useful for liquid ventilation therapy.
  • PLV partial liquid ventilation
  • LiquiVent® Alliance Pharmaceutical Corp., San Diego, CA.
  • a closed rebreathing circuit designed to minimize the evaporative loss of a ventilation fluid such as perflubron, during partial liquid ventilation.
  • a bag-in-box system separates the lungs from the ventilator with perflubron vapor circulating between the bag and the lungs, in a closed rebreathing system.
  • the box When the box is pressurized by the gas tidal volume of the ventilator, the bag delivers a tidal volume to the patient's lung.
  • the system according to the present invention may provide special safety relief valves, a volume controller, an oxygen controller, a design that maximizes ventilator tidal volume control, or any combination of the above improvements.
  • Figure 1 is a block diagram of the closed rebreathing circuit according to the present invention, especially showing the safety relief valves.
  • Figure 2 is a block diagram of the closed rebreathing circuit according to the present invention, especially showing the volume controller and the oxygen controller.
  • Figure 3 is the experimental protocol for the in vivo experiments detailed in Example 5.
  • Figures 4A-C are a series of graphs of actual vs. target tidal volumes for various lung compliances with the ventilator in the volume control mode.
  • the x axis shows the tidal volume set on the ventilator.
  • the y axis shows the tidal volume delivered to the test lung, as measured by the airway flowmeter (COSMO+, Novametrix, Wallingford, CT).
  • the solid line shows the line of identity.
  • the circles show the tidal volume delivered to the test lung without the breathing circuit in place and the diamonds show the volume delivered with the breathing circuit in place.
  • Figures 5A-C are a series of graphs of peak pressures measured at the ventilator (x axis) vs peak pressure measured at the test lung (COSMO) (y axis), with and without the closed breathing system in use, with the ventilator in the volume control mode.
  • the diamonds show the peak pressure when the breathing circuit is in use.
  • the circles show the peak airway pressure, when the ventilator is connected directly to the test lung.
  • Figure 6 is a block diagram of the closed rebreathing circuit according to the present invention, especially showing the novel design that minimizes the difference between the tidal volume delivered by the ventilator and the tidal volume received by the patient.
  • a closed rebreathing circuit comprising a ventilator, an airtight container in fluid communication with the ventilator, a bag contained within the airtight container, in pressure communication but not in fluid communication with the airtight container, and breathing circuit in fluid communication with said bag, said breathing circuit being adapted for connection to an air-breathing patient; a CO 2 absorber situated within the breathing circuit so as to absorb CO 2 expired by the patient, and an oxygen controller.
  • the oxygen controller in the invention rebreathing circuit measures the difference in oxygen concentration between the ventilator and the breathing circuit, and adjusts the oxygen concentration in the breeathing circuit to match the oxygen concentration in the ventilator.
  • FIG. 1 An embodiment of the invention rebreathing circuit is shown in Figure 1 herein.
  • the invention closed rebreathing system 10 is designed to circulate a ventilation liquid between the patient's lungs and a standard ICU ventilator.
  • the system 10 is essentially a bag 16 in a box 14 that serves to separate a patient 30 from a ventilator 12.
  • the patient 30 is connected to the box 14 by an expiratory hose 26 and an inspiratory hose 28.
  • the patient 30 is intended to be human but may be any other animal that breathes air.
  • the hoses 26 and 28 are preferably 22 mm hoses (for a human patient), although any appropriate hoses may be used.
  • the materials used in fabrication of the invention device are compatible with any respiratory promoter, such as a ventilation gas or partial liquid ventilation substance.
  • Particularly preferred fabrication materials are generally compatible with fluorochemicals.
  • such materials include, but are not limited to cellulose acetate, polypropylene, polyurethane, polyethylene (e.g., HDPE), polyvinylidene difluoride, stainless steel, Teflon FEP, Teflon PTFE, Teflon, Viton, Viton A, acrylic, brass, chrome-plated materials, Cycolac ABS, polyvinyl chloride, polyvinylidene difluoride, rubber, polycarbonate, polyester, and high density polyethylene.
  • fluorochemical any fluorinated carbon compound with appropriate physical properties of biocompatibility. These properties are generally met by fluorochemicals having low viscosity, low surface tension, low vapor pressure, and high solubility for oxygen and carbon dioxide, making them able to readily promote gas exchange while in the lungs. For example, it is preferred that the fluorochemical have at least 3 or 4 carbon atoms and/or that its vapor pressure at 37°C is less than 760 Torr.
  • the fluorochemical may be made up of atoms of carbon and fluorine, or may be a fluorochemical having atoms other than just carbon and fluorine, e.g., bromine or other nonfluorine substituents. Those skilled in the art will appreciate that the range of compatible fluorochemicals is substantially broadened by the present invention.
  • one of the major advantages of the present invention is that closed-circuit ventilation allows the extended therapeutic use of fluorochemicals that were previously too volatile to use effectively.
  • some volatile fluorochemicals were used for short term drug therapy where pulmonary retention time was not critical.
  • high vapor pressure fluorochemicals may be used effectively as they are not lost to the outside atmosphere. That is, the closed-circuit systems of the present invention promote substantial equilibrium for most ventilating gas components including volatile fluorochemicals. Accordingly, steady pulmonary levels of these fluorochemicals are rapidly reached and easily maintained using the novel closed-circuit systems described herein.
  • the selected fluorochemical will be able to cover a substantial amount of pulmonary tissue with relatively little volume. Adequate coverage of the lung surface is desirable for restoring oxygen and carbon dioxide transfer and for lubricating the lung surfaces to minimize further pulmonary trauma.
  • the ability of a given substance to cover a measured surface area can be described by its spreading coefficient.
  • the spreading coefficients for fluorochemicals can be expressed by the following equation:
  • S (o on w) represents the spreading coefficient
  • g interfacial tension
  • w/a water/air
  • w/o water/oil
  • o/a oil/air
  • Fluorochemicals exhibiting a positive spreading coefficient will tend to spread over the respiratory membrane spontaneously. Fluorocarbons having spreading coefficients of at least one are particularly preferred. If the spreading coefficient is negative, the compound will tend to remain as a lens on the membrane surface.
  • Brominated fluorochemicals include 1-bromo-heptadecafluoro-octane (C 8 F Br, sometimes designated perfluorooctyl bromide or "PFOB"), 1-bromopenta-decafluoroheptane (C 7 F 15 Br), 1-bromotrideca fluorohexane (C 6 F 13 Br, sometimes known as perfluorohexyl bromide or "PFHB”), and the like.
  • PFOB perfluorooctyl bromide
  • PFHB 1-bromotrideca fluorohexane
  • Other brominated fluorochemicals are disclosed in US Patent No. 3,975,512 to Long, which is incorporated herein by reference in its entirety.
  • closed rebreathing circuit fluorochemicals having nonfluorine substituents, such as perfluorooctyl chloride, perfluorooctyl hydride, and similar compounds having different numbers of carbon atoms.
  • fluorochemicals contemplated in accordance with this invention include perfluoroalkylated ethers or polyethers, such as (CF 3 ) 2 CFO(CF 2 CF 2 ) 2 OCF(CF 3 ) 2 , (CF 3 ) 2 CFO-(CF 2 CF 2 ) 3 OCF(CF 3 ), (CF 3 )CFO(CF 2 CF 2 )F, and (CF 3 ) 2 CFO(CF 2 CF 2 ) 2 F, (C 6 F 13 ) 2 O, and the like.
  • fluorochemical-hydrocarbon compounds contemplated for use in the invention closed rebreathing circuit include for example, compounds having the general formula C n F 2n+1 -C n .F 2n .
  • n and n' are the same or different and are from about 1 to about 10 (so long as the compound is a liquid at room temperature).
  • esters, thioethers, and other variously modified mixed fluorochemical-hydrocarbon compounds are also encompassed within the broad definition of "fluorochemical" liquids suitable for use in the present invention.
  • fluorochemicals are also contemplated and are considered to fall within the meaning of "fluorochemical liquids” as used herein. Additional “fluorochemicals” contemplated are those having properties that would lend themselves to pulmonary gas exchange including FC-75, FC-77, RM-101, Hostinert 130, APF-145, APF-140, APF-125, perfluorodecalin, perfluorooctylbromide, perfluorobutyl-tetrahydrofuran, perfluoropropyl-tetrahydropyran, dimethyl - adamantane, trimethyl-bicyclo-nonane, and mixtures thereof.
  • preferred fluorochemicals are characterized by having: (a) an average molecular weight range from about 350 to 570; (b) viscosity less than about 5 centipoise at 25°C; (c) boiling point greater than about 55°C; (d) vapor pressure in the range from about 5 to about 75 Torr, and more preferably from about 5 to about 50 Torr, at 25°C; (e) density in the range of about 1.6 to about 2 gm/cm ; and (f) surface tensions (with air) of about 12 to about 20 dyne/cm.
  • Perflubron is the presently preferred fluorochemical for use in the present invention.
  • gases and liquid vapors may also be used in combination with the ventilation liquids in the practice of the present invention.
  • pharmaceutical agents as respiratory agents, antibiotics, antivirals, mydriatics, antiglaucoma agents, anti-inflammatories, antihistaminics, antineoplastics, anesthetics, ophthalmic agents, cardiovascular agents, active principles, nucleic acids, genetic material, immunoactive agents, imaging agents, immunosuppressive agents, gastrointestinal agents, and the like, as well as combinations thereof may be added to the ventilation liquid circulated by the invention closed rebreathing system.
  • exemplary pharmaceutical agents useful for addition to the ventilation liquid(s) include anti-inflammatory agents such as the glucocorticosteroids (i.e. cortisone, prednisone, prednisolone, dexamethasone, betamethasone, Beclomethasone diproprionate, Triamcinolone acetonide, Flunisolide), xanthines (i.e. theophylline, caffeine), chemotherapeutics (i.e. cyclophosphamide, lomustine, methotrexate, cisplatin, taxane derivatives), antibiotics (i.e.
  • anti-inflammatory agents such as the glucocorticosteroids (i.e. cortisone, prednisone, prednisolone, dexamethasone, betamethasone, Beclomethasone diproprionate, Triamcinolone acetonide, Flunisolide), xanthines (i.e. theophylline,
  • bronchodilators such as the B 2 -agonists (i.e. adrenaline, isoprenaline, salmeterol, albuterol, salbutamol, terbutaline, formoterol), surfactants, and the like.
  • B 2 -agonists i.e. adrenaline, isoprenaline, salmeterol, albuterol, salbutamol, terbutaline, formoterol
  • surfactants and the like.
  • Still other exemplary embodiments include a/B adrenergic blockers (i.e. Normodyne®, Trandate®), angiotensin converting enzyme inhibitors (i.e.
  • Vasotec® antiarrhythmics, beta blockers, calcium channel blockers, ionotropic agents, vasodilators, vasopressors, anesthetics (i.e. morphine), ophthalmic agents (i.e. Polymyxin B, Neomycin, Gramicidin), the guanosine nucleoside analog, 9-(l,3- dihydroxy-2-propoxymethyl)guanine, otherwise known as Ganciclovir or DHPG, and the like.
  • ionotropic agents i.e. Polymyxin B, Neomycin, Gramicidin
  • ophthalmic agents i.e. Polymyxin B, Neomycin, Gramicidin
  • the guanosine nucleoside analog 9-(l,3- dihydroxy-2-propoxymethyl)guanine, otherwise known as Ganciclovir or DHPG, and the like.
  • One-way valves 22 in each hose 26 and 28 ensure unidirectional flow through a CO 2 absorber 24 that is inside the box 14.
  • the CO 2 absorber 24 preferably contains barium hydroxide lime, mesh 4 to 8 (BaraLyme , Allied Healthcare Products, Inc.), but any material that absorbs CO 2 sufficiently well may be used instead, such as ThermaSorbTM (Raincoat, Inc., Louisville, KY), SodasorbTM (BOC Gases, NJ), Dry denTM (Dry den Inc., Indianapolis, IN), and the like.
  • the ventilator 12 may be of almost any known model.
  • Examples of commercially available ventilators that are compatible with the present invention include, but are not limited to, Servo 300 and Servo 900C (Seimens Elema, Shaumburg, 111.), Infant Star and Adult Star (Star Products, San Diego, CA), Bear 1,2,3 (Bear Medical, Browns, CA), Puriton Bennett 7200, (Puriton-Bennett Corp., Carlsbad, CA) Baby Bird 2 (Bird Corp., CA), Healthdyne Infant Ventilator, Evita (Drager), or the like.
  • the Servo 900C is preferred.
  • the ventilator 12 is connected to the box 14 by appropriate hosing or other means of gaseous communication.
  • the box 14 may be of a wide variety of shapes and/or sizes, as long as it accommodates the bag 16 and other necessary components as described herein. It is preferred that the box 14 have as small an internal volume as possible, so as to minimize the discrepancy between the tidal volume set on the ventilator and the tidal volume actually delivered to the patient 30 (see infra).
  • the box 14 is a 3.5 liter Plexiglas cylinder which surrounds a 2.0 liter rebreathing bag (Anesthesia Associates, Inc., San Marcos, CA).
  • the bag 16 may also be of a wide variety of shapes and sizes, as long as it is of adequate size for the maximum tidal volume required by the patient 30.
  • the bag 16 has associated therewith first and second safety relief valves 18 and 20.
  • the first valve 18 vents gas from the bag 16 into the volume directly connected to the ventilator 12, should the bag 16 become over-distended (i.e., the pressure in the bag 16 becomes too high).
  • the second valve 20 lets the ventilator 12 bypass the bag 16, to fill the lung during inspiration, should the bag 16 have too low a volume, or become empty.
  • a presently preferred valve is an adjustable positive end-expiratory pressure (PEEP) Valve (7620, Vital Signs, Inc., Totowa, NJ).
  • PEEP positive end-expiratory pressure
  • the valves 18 and 20 may also be selected from many other known commercially available valves, such as a Popoff valve (Halkey Roberts, St.
  • valves 18 and 20 may be designed with a preset pressure point, or may be adjustable. In either case, it is presently preferred that both valves 18 and 20 be set to about 2.0 cm H 2 O. However, depending upon the requirements of the patient 30 and other factors, those of skill in the art understand that a wide variety of settings may be used.
  • the closed rebreathing system 10 of the present invention also includes a volume controller 32, which is shown in Figure 2.
  • the volume controller 32 ensures that a minimum of one tidal volume is in the bag 16 at the end of expiration, such that a full tidal volume will be available for delivery to the patient 30 for the next inspiration.
  • the volume controller 32 includes a computer or other control means (not shown) that controls the action of the other components as described below.
  • a sensor 34 measures the pressure in the bag 16, and compares it to the pressure in the box 14 outside the bag 16.
  • the sensor 34 may be selected from a variety of commercially available devices, such as a Sensym sensor (Sunnyville, CA), a Micro Switch pressure transducer (Freeport, IL), a Validyne sensor (Northridge, CA), an IC Sensors sensor (Milpitas, CA), a Millar sensor (Houston, TX), and the like.
  • a Sensym sensor Sennyville, CA
  • a Micro Switch pressure transducer Freeport, IL
  • a Validyne sensor Northridge, CA
  • an IC Sensors sensor Milpitas, CA
  • a Millar sensor Houston, TX
  • the volume controller 32 thus acts by adding a bolus of gas to partially prefill the bag 16 before the next breath occurs (a threshold of 0.5 cm H 2 O is preferably used when the oxygen concentration in the patient circuit is too low so that more than one bolus is added per breath, to speed the transition to normal).
  • the volume controller 32 meters the added gas by first opening a valve 36
  • valves 36 and 40 may be of any suitable design, but are preferably a Model SY114 (SMC Pneumatics, Inc., Indianapolis, IN). Other suitable valves include a Minimatic valve (Clippard, Cincinnati, OH), as well as various valves made by Lee (Los Angeles, CA), Numatics (Highland, MI), Deltrol (Bellwood, IL), and the like.
  • Opening valve 36 or 40 fills a reservoir 44 having a volume (V res ) to the pressure of the oxygen source 38 or air source 42, whichever is used.
  • V res volume
  • the reservoir 44 may be essentially any container of the appropriate volume that can repeatedly withstand the necessary pressures, and is equipped for connection to multiple gas lines.
  • the reservoir may also be filled with copper wool or other thermally conductive materials so as to enable the temperature of the gas to stabilize rapidly.
  • the reservoir 44 is a NAR 1000 pressure regulator (SMC, Japan).
  • Other suitable reservoirs 44 include a MAT Inline Volume Chamber (Clippard, Cincinnati, OH), and the like.
  • the volume controller 32 opens valve 36 or 40 for about 460 msec to allow the reservoir 44 to fill to the supply pressure. The volume controller 32 then closes all valves for about 40 msec to allow the pressure to stabilize (P ⁇ n, Absolute Pressure), opens valve 46 for about 460 msec to empty the reservoir 44, and finally closes all valves for 40 msec to let the pressure stabilize again (P empty , Absolute Pressure).
  • the gas volume delivered (Vb) is:
  • Vb Kes (Pfull/P empty) (1)
  • the gas volume delivered is directly proportion to P j _, n and inversely proportional to P empt) ,.
  • the closed rebreathing system 10 of the present invention also includes an oxygen controller 48, which is also shown in Figure 2.
  • the oxygen controller 48 measures the oxygen concentration delivered by the ventilator 12 and maintains the oxygen concentration in the breathing circuit at the same level.
  • the oxygen controller 48 includes a computer or other control means (not shown) that controls the action of the other components as described below.
  • the oxygen controller 48 opens valve 50 and turns on a sampling pump 52 to draw 600 ml/min of gas from the ventilator 12 to an oxygen sensor 54.
  • the sampling pump 52 may be selected from a wide variety of commercially available devices, including a Model 3003 pump (ASF Thomas, Norcross, GA).
  • the oxygen sensor 54 may also be selected from a wide variety of commercially available devices, such as those made by Ceramatec®, Inc. (Salt Lake City, UT), Hudson (Temecula, CA), Servomex (Crowborough, East Wales, UK), MSA (Pittsburgh, PA), Oxigraph (Palo Alto, CA), and the like.
  • valve 50 After about 10 sec the oxygen controller 48 closes valve 50 and waits about 15 seconds for the oxygen sensor 54 to stabilize, then reads the oxygen level. Next, the oxygen controller 48 opens valve 56 to draw gas from the breathing circuit (again, preferably using sampling pump 52). When sampling from the breathing circuit, the sampled gas is preferably returned to the breathing circuit.
  • the gas entering the oxygen sensor is relatively dry, as many oxygen sensors are more accurate with dry air. Also, continued exposure to wet air can cause long term problems with some oxygen sensors.
  • the gas moving from the breathing circuit into the oxygen sensor is passed through a section of nafion tubing. This special tubing is made from a material that removes the liquid water from the gas.
  • the gas is passed through or over a chemical material that absorbs or adsorbs the water vapor.
  • the gas is passed through a condensor, such as, for example, a peltier cooling device, that cools the gas and causes the excess water vapor to condense (and collects the condensed water).
  • the pump 58 remains on until a calculated volume (V out ) has been removed.
  • the volume of gas removed is calculated by equation (2) below:
  • the volume controller 32 will sense the loss of volume and replace it with air, thus lowering the oxygen concentration to the desired level.
  • the oxygen controller 48 If the breathing circuit oxygen concentration and the ventilator oxygen concentration are within 3 vol% of each other, the oxygen controller 48 is idle and the volume controller 32 adds oxygen when prefilling the bag, thus making up for oxygen consumption by the patient 30. If the breathing circuit oxygen concentration is more than 3 vol% lower than the ventilator concentration, the oxygen controller 48 turns on pump 58 to draw N 2 out of the patient breathing circuit. The volume removed is calculated by Equation (3) below:
  • the volume controller 32 will add O 2 to replace the volume removed, thus raising the oxygen concentration.
  • the oxygen controller 48 Upon start-up and at pre-selected (preferably five minute) intervals, the oxygen controller 48 automatically calibrates the oxygen sensor 54 by filling the sensor with either 100% oxygen or air (21% oxygen). The sensor output is allowed to stabilize in the presence of each gas, thus resulting in a two-point calibration.
  • the closed rebreathing circuit provides separation between the lungs, partially filled with the ventilation fluid, such as perflubron, and an ICU ventilator.
  • Perflubron remains in the lungs and evaporative loss is minimized due to the recirculation of breathing gas within the system.
  • the ventilator will remain fully functional in all modes, trigger properly, and hold PEEP.
  • the closed rebreathing circuit described herein differs from traditional anesthesia breathing circuits in the use of two safety relief valves, one to allow gas to move from the ventilator into the breathing bag any time the bag is underfilled, and a second relief valve to prevent the bag from becoming too full (applying inadvertent PEEP).
  • the circuit also has two automatic controllers, one maintains the breathing circuit oxygen concentration at the same level as the concentration set on the ventilator (making the device somewhat transparent to the ICU user), and the second maintains the bag end expiratory volume. Both these tasks must be performed manually with traditional anesthesia machines.
  • the design of the present invention allows the use of standard ICU ventilators so that ventilator modes such as pressure control, pressure support, and synchronized intermittent mandatory ventilation (SIMV) can be used during liquid ventilation.
  • SIMV synchronized intermittent mandatory ventilation
  • the closed rebreathing system can also provide a quantitative measure of oxygen consumption and leakage. The amount of oxygen metered into the breathing circuit is a measure of the subject's oxygen consumption, whereas the amount of nitrogen is a measure of the circuit leakage.
  • the delivered tidal volume does not match the tidal volume set on the ventilator.
  • the delivered tidal volume can be up to 30% less than expected. It is therefore recommended that delivered tidal volumes be monitored at the airway and the ventilator set accordingly.
  • CO 2 absorbers as used in the closed rebreathing system, are not commonly used in the ICU. They must be changed every eight to twelve hours resulting in an additional nursing task. Thus, a capnometer is recommended to monitor the inspired CO 2 concentration and an alarm will sound should the CO 2 absorber become depleted.
  • the user must manually intervene to make a rapid change as needed in the oxygen concentration.
  • the automatic controller takes up to seven minutes to withdraw gas from the circuit and replace it with oxygen before the desired concentration is reached. With the manual override, the user can change the concentration within two minutes.
  • Several safety features are present in the system design. Compressed air and oxygen cannot inadvertently enter the breathing circuit unless two normally closed valves fail open at the same time. If the electrical power is lost, a needle valve provides for 500 ml of oxygen to flow to the breathing circuit, to keep the oxygen concentration constant.
  • the safety relief valves allow the ventilator to continue ventilation, even if the breathing bag is collapsed.
  • Figure 6 depicts another embodiment of the closed rebreathing system according to the present invention.
  • This embodiment is designed to minimize the amount of compressible volume surrounding the bag 16, thus reducing ventilator interaction artifacts.
  • This is preferably achieved by the use of a gas volume conserving square bellows 16 '/square box 4' system, and by the use of an adjustably inflatable chamber within the closed rebreathing system which automatically adjusts system compression volume to a level always slightly above the current ventilator tidal volume setting.
  • the liquid perfluorocarbon enters at port 64.
  • a smaller form factor CO 2 cartridge 24' may be mounted external to the closed rebreathing system to further reduce system compression volume and also to simplify cartridge changeout.
  • the device pneumatics can be mounted above the system electronics 64 to enable an automatic warming of the vapor-containing spaces, reducing condensation deposition within the device. Finally, tilting of the bellows assembly 16' will prevent liquid accumulation within the device.
  • a lung simulator was used to test the performance of the controllers.
  • the breathing circuit was connected to a test lung (TTL Michigan Instruments, Inc.) with 1.5 meter breathing hoses.
  • the test lung airway resistance was set to 5.6 cm H 2 O/l/sec.
  • the compliance was set to 0.1 1/cm H 2 O (normal adult), 0.07, or 0.03 (stiff lung filled with perflubron).
  • Carbon dioxide was added to the test lung at 200 ml/min to simulate CO 2 production.
  • a capnometer and flowmeter were placed in the airway, at the inlet to the test lung, to measure tidal volume and airway pressure (COSMO+, Novametrix, Wallingford, CT).
  • COSMO+ tidal volume and airway pressure
  • the response time of the oxygen controller was measured by resetting the Siemens oxygen blender from 70% to 80% and recording the time until the breathing circuit oxygen concentration reached 79% (90% change from old to new value). The response time was measured from 70%-80%, 80%-90%, 90%- 100%, 100%-90%, 90%-80%, and 80%-70%.
  • Table 1 lists the 0-90% response times and overshoot (voP/o) of the oxygen for a rapid step change in oxygen concentration in the breathing circuit following a rapid change in the ventilator blender setting.
  • the additional trigger delay introduced by the breathing circuit was measured. Negative pressure in the test lung was measured by manually lifting the bellows. The trigger delay was the time between the onset of the negative pressure spike in the test lung and the onset of the positive pressure rise in the airway caused by the ventilator cycle. Twelve measurements were taken with and without the breathing circuit in place.
  • adding the closed circuit increased the trigger delays from 140 msec to 200 msec.
  • the protocol was as follows: anesthetized pigs (male or female, 40-50 kg) were preanesthetized with ketamine (40 mg/kg), atropine (50_mg/kg), and acepromazine (1.2 mg/kg) IM. Pentobarbital sodium (Nembutal®, 50 mg/ml) was administered via ear vein and titrated to effect. Buprenorphine (0.01 mg/kg) and Diazepam (0.6 mg/kg) were administered IM. Pigs were then intubated with a modified (extended by 10-11 cm) 6.0 jet- ventilation endotracheal (ET) tube (Mallinckrodt Medical, Inc., St.
  • ET jet- ventilation endotracheal
  • trachea was tied proximal to the balloon cuff of the endotracheal tube to prevent slippage and possible leakage of perflubron.
  • Electrocardiogram needles were placed to monitor heart rate and a carotid artery catheter was placed for measurement of blood gases and systemic pressure.
  • a jugular vein catheter was placed for administration of fluids (PlasmaLyte, hydration target at 25 mL/kg followed by a maintenance rate of 5 mL/kg/hr), anesthesia, paralytic, and other drug interventions (e.g. sodium bicarbonate, lidocaine).
  • a Swan-Ganz catheter was placed via jugular vein for monitoring of pulmonary pressures and core body temperature.
  • Each animal was dosed supine with a functional residual capacity (FRC) volume of room temperature perflubron (i.e., they were filled until a meniscus was observed in the proximal ET tube, with dose maintained at ⁇ 30 ml/kg perflubron).
  • the liquid was introduced through the distal sideport to ET tube at 1 -2 ml/kg/min. No redosing of perflubron occurred throughout the remainder of the 12 hour study.
  • Monitoring during the study included arterial blood gases (ABG), mean arterial pressure (MAP), heart rate (HR), and central venous pressure (CVP) every hour.
  • ABS arterial blood gases
  • MAP mean arterial pressure
  • HR heart rate
  • CVP central venous pressure
  • BP blood pressure
  • PEEP positive end-expiratory pressure
  • pulmonary pressures artery and wedge
  • Weight of Perflubon Total weight - Weight of (4) only in lungs of lungs “dry” lungs
  • Q is Evaporative rate of Control group
  • R D is Evaporative rate with device
  • Evaporative rate was determined using the lung weight technique described to assess perflubron loss over time. Efficiency was calculated assuming that a small quantity of perflubron (about 45 ml) lost due to condensation ("rain out") in the patient circuit could, under conditions of conventional circuit heating, be recovered. Table 2 shows Perflubron dose consumption in swine projected over a three day PLV treatment.
  • Patient supplemental doses is the amount of perflubron projected over the course of a 72 hour treatment.
  • the additional perflubron used is the amount lost to evaporation.

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  • Health & Medical Sciences (AREA)
  • Pulmonology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Engineering & Computer Science (AREA)
  • Anesthesiology (AREA)
  • Biomedical Technology (AREA)
  • Emergency Medicine (AREA)
  • Hematology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Ce système clos de réinhalation constitue un moyen sûr et efficace de ventilation par liquide qui, réduisant à leur minimum les pertes en fluide de ventilation en phase vapeur, permet d'abaisser la consommation dudit fluide et réduit au maximum le travail lié à un nouveau dosage. Il est possible d'employer un ventilateur ICU fonctionnant en modes normaux si l'utilisateur corrige la réduction de volume respiratoire (associé à la perte de la compliance pulmonaire) et intervient manuellement, si nécessaire, pour augmenter rapidement la concentration en oxygène. Ce circuit fermé permet de mesurer la consommation d'oxygène et sa déperdition.
PCT/US1999/012133 1998-06-01 1999-06-01 Systeme clos de reinhalation permettant de conserver les memes dosages lors d'une ventilation par liquide Ceased WO1999062581A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU44111/99A AU4411199A (en) 1998-06-01 1999-06-01 Closed rebreathing system for dose maintenance during liquid ventilation

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US8752998P 1998-06-01 1998-06-01
US60/087,529 1998-06-01

Publications (2)

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WO1999062581A3 WO1999062581A3 (fr) 2000-03-09

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Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003099364A1 (fr) * 2002-05-23 2003-12-04 Art Of Xen Limited Systeme d'alimentation de gaz
GB2406282A (en) * 2003-07-03 2005-03-30 Alexander Roger Deas Self-contained underwater re-breathing apparatus having a shortened breathing hose
WO2006021182A1 (fr) * 2004-08-21 2006-03-02 Viasys Healthcare Gmbh Sac reservoir de gaz, boitier distributeur, masque respiratoire et procede de respiration
CN100402103C (zh) * 2003-05-22 2008-07-16 重庆海扶(Hifu)技术有限公司 排液通气呼吸系统
US7503325B2 (en) 2003-09-30 2009-03-17 The Research Foundation Of State University Of New York Device and method of partially separating gas
WO2010133843A2 (fr) 2009-05-19 2010-11-25 Art Of Xen Limited Ventilateur respiratoire
CN102691850A (zh) * 2012-05-30 2012-09-26 张秀英 一种密闭液循环回路的容积调节器
EP2303375A4 (fr) * 2008-05-08 2014-03-05 Edward Masionis Système portatif de ventilateur de maintien des fonctions vitales
CN105498056A (zh) * 2015-12-24 2016-04-20 聂文军 一种呼吸循环仪

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CS252705B1 (en) * 1984-07-03 1987-10-15 Ondrej Brychta Anaestesiological circuit with backward inspiration with injector of volatile anaestetic agents
GB9511651D0 (en) * 1995-06-08 1995-08-02 Univ Wales Medicine Blood Volume Measurement
AUPN381195A0 (en) * 1995-06-26 1995-07-20 Techbase Pty. Ltd. Bag in pressure chamber arrangement for use in anaesthesia and resuscitation apparatus
US6041777A (en) * 1995-12-01 2000-03-28 Alliance Pharmaceutical Corp. Methods and apparatus for closed-circuit ventilation therapy
US5806513A (en) * 1996-10-11 1998-09-15 Ohmeda Inc. Method and apparatus for controlling a medical anesthesia delivery system
FR2755017B1 (fr) * 1996-10-30 1998-12-18 Taema Dispositif d'assistance respiratoire

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2005526576A (ja) * 2002-05-23 2005-09-08 アート オブ ゼン リミテッド ガス供給システム
WO2003099364A1 (fr) * 2002-05-23 2003-12-04 Art Of Xen Limited Systeme d'alimentation de gaz
CN100402103C (zh) * 2003-05-22 2008-07-16 重庆海扶(Hifu)技术有限公司 排液通气呼吸系统
GB2406282A (en) * 2003-07-03 2005-03-30 Alexander Roger Deas Self-contained underwater re-breathing apparatus having a shortened breathing hose
US7503325B2 (en) 2003-09-30 2009-03-17 The Research Foundation Of State University Of New York Device and method of partially separating gas
WO2006021182A1 (fr) * 2004-08-21 2006-03-02 Viasys Healthcare Gmbh Sac reservoir de gaz, boitier distributeur, masque respiratoire et procede de respiration
EP2303375A4 (fr) * 2008-05-08 2014-03-05 Edward Masionis Système portatif de ventilateur de maintien des fonctions vitales
WO2010133843A2 (fr) 2009-05-19 2010-11-25 Art Of Xen Limited Ventilateur respiratoire
JP2012527280A (ja) * 2009-05-19 2012-11-08 アート オブ ゼン リミテッド 人工呼吸装置
WO2010133843A3 (fr) * 2009-05-19 2011-01-06 Art Of Xen Limited Ventilateur respiratoire
US9138551B2 (en) 2009-05-19 2015-09-22 Art Of Xen Limited Ventilator apparatus
CN102691850A (zh) * 2012-05-30 2012-09-26 张秀英 一种密闭液循环回路的容积调节器
CN105498056A (zh) * 2015-12-24 2016-04-20 聂文军 一种呼吸循环仪

Also Published As

Publication number Publication date
AU4411199A (en) 1999-12-20
WO1999062581A3 (fr) 2000-03-09

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